Approaches to Second-Line Therapy After Checkpoint Inhibitor Failure

The faculty address management after progression on checkpoint inhibitor monotherapy in patients who are not candidates for further surgery or radiation. Dr In outlines his approach to second-line therapy, including EGFR-directed treatment with cetuximab, which retains activity in cutaneous squamous cell carcinoma, and the alternative option of panitumumab. The faculty discuss dosing and scheduling considerations, including weekly and every 2 week EGFR-directed regimens compared with the every 3 week schedule used for immunotherapy, and how those logistics affect older patients traveling for infusions. Dr Whitman raises combination approaches under investigation, referencing a randomized phase 2 study evaluating avelumab with cetuximab compared with avelumab alone in advanced disease. Both faculty encourage clinical trial enrollment where available and note that cytotoxic chemotherapy remains a consideration in selected patients, though with limited durability compared with checkpoint blockade in the frontline setting.